The C57BL/6 nu/nu lpr/lpr mouse. II. Pedigree and preliminary characteristics.

A short-cut procedure is described which allows to construct new mouse strains which are double congenic for the nu gene (nude, athymic) and the lpr gene (lymphoproliferation). Since both nu and lpr genes are recessive and that the lack of thymus impairs the expression of the lpr phenotype in euthymic animals, the homozygosity of nude animals for the lpr gene was based on the results of progeny analyses. A C57BL/6 nu/nu lpr/lpr (B6 nu/nu, lpr/lpr) was made in four generations starting from C57BL/6 nu/nu (B6 nu/nu) and C57BL/6 lpr/lpr (B6 lpr/lpr). This possibility stems from an absence of close linkage of the nu and lpr genes. The emergence of the nude phenotype at the different steps of the pedigree was less frequent than expected if the nu and lpr genes were completely independent. However, this is probably due to environmental factors causing a negative selection of nude littermates. The B6 nu/nu lpr/lpr represents a new important tool for the study of how the thymus modulates the lpr gene controlled acceleration of autoimmunity. Preliminary data indicate that the lpr phenotype (massive lymphadenopathy and splenomegaly accompanied by severe auto-immune disease with features of systemic lupus erythematosus) appears when a thymus is grafted to the B6 nu/nu lpr/lpr.